Fig. 5: Lpc-EV treatment restored the Aβ42-induced downregulation of Aβ-degrading enzymes, and suppressed Aβ accumulation in Tg-APP/PS1 mice. | Experimental & Molecular Medicine

Fig. 5: Lpc-EV treatment restored the Aβ42-induced downregulation of Aβ-degrading enzymes, and suppressed Aβ accumulation in Tg-APP/PS1 mice.

From: Lactobacillus-derived extracellular vesicles counteract Aβ42-induced abnormal transcriptional changes through the upregulation of MeCP2 and Sirt1 and improve Aβ pathology in Tg-APP/PS1 mice

Fig. 5

a, b Photomicrographs showing the thioflavin S-stained parietal cortex, hippocampus, and piriform cortex (a) of Tg-APP/PS1 mice, and Tg-APP/PS1 mice treated with Lpc-EV at 8 months of age. Higher magnification of the boxed areas in the parietal cortex (b). Lpc-EV was orally administered at a dose of 2.27 mg/kg/day, as depicted in Fig. 3A. c, d Quantification of the number of plaques (c) and total plaque area (d) in the parietal cortex, hippocampus, and piriform cortex of Tg-APP/PS1 mice, and Tg-APP/PS1 mice treated with Lpc-EV. n = 9 animals per group. Plaque numbers: CA1, t(16) = 3.122, p = 0.0066; CA3, t(16) = 5.968, p < 0.0001; DG, t(16) = 1.597, p = 0.1298. Plaque area; CA1, t(16) = 2.016, p = 0.061; CA3, t(16) = 3.034, p = 0.0079; DG, t(16) = 1.300, p = 0.2121. e Expression levels of Mmp-2, Mmp-9, tPA, Ide, Nep, and Lrp1 in the hippocampi of WT mice, Tg-APP/PS1 mice, and Tg-APP/PS1 mice treated with Lpc-EV. n = 8 animals per group. Mmp-2, F(2,21) = 43.29; p < 0.0001; Mmp-9, F(2,21) = 67.69, p < 0.0001; tPa, F(2,21) = 7.643, p = 0.0115; Ide, F(2,21) = 37.29, p < 0.0001; Nep, F(2,21) = 38.69, p < 0.0001; Lrp1, F(2,21) = 44.16, p < 0.0001. f Expression levels of Mmp-2, Mmp-9, uPA, Ide, Nep, and Lrp1 in HT22 cells (CON), HT22 cells treated with Lpc-EV (10 μg/ml), HT22 cells treated with Aβ42 (1 μM), and HT22 cells treated with Aβ42 plus Lpc-EV. n = 8 per group. Mmp-2, F(3,28) = 49.54, p < 0.0001; Mmp-9, F(3,28) = 13.13, p = 0.0004; tPa, F(3,28) = 0.9267, p = 0.4505; Ide, F(3,28) = 4.003, p = 0.0345; Nep, F(3,28) = 7.959, p = 0.0035; Lrp1, F(3,28) = 0.4260, p = 0.7380. g, h Expression levels of Mmp-2, Mmp-9, uPA, Ide, Nep, and Lrp1 in HT22 cells (CON), HT22 cells treated with Aβ42, and HT22 cells treated with Aβ42 plus the indicated siRNA; siRNA-MeCP2 (g) and siRNA-Sirt1 (h). n = 8 per group. siRNA-MeCP2; Mmp-2, F(3,28) = 10.49, p = 0.0011; Mmp-9, F(3,28) = 17.91, p < 0.0001; tPa, F(3,28) = 0.7474, p = 0.5444; Ide, F(3,28) = 1.777, p = 0.2050; Nep, F(3,28) = 8.157, p = 0.0032; Lrp1, F(3,28) = 0.9080, p = 0.4659. siRNA-Sirt1; Mmp-2, F(3,28) = 45.19, p < 0.0001; Mmp-9, F(3,28) = 6.416; p = 0.0077; tPa, F(3,28) = 1.127, p = 0.3619; Ide, F(3,28) = 3.498, p = 0.0497; Nep, F(3,28) = 12.95, p = 0.0005; Lrp1, F(3,28) = 3.338, p = 0.0561. Data are presented as the mean ± SEM. *p < 0.05; **p < 0.01 (Student’s t-test; one-way ANOVA followed by the Newman‒Keuls post hoc test; and two-way ANOVA followed by the Bonferroni post hoc test).

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